NOVEL EXTRACELLULAR PROTEINS IN AXON GUIDANCE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The cells of our nervous system are separated by large distances and must be connected to one another by wiring capable of carrying electrical or chemical signals. The individual fibers are known as axons, and in the early embryo they have to navigate large distances to connect up the nervous system. Cells sense their environment through proteins, known as receptors, on their surfaces that bind signals in their environment. Few signals and receptors for axons are currently known. One class is the Netrin protein family that stimulates growing nerves in the developing spinal cord, as well as other cell types including blood vessels. Through genetic screens, we have identified a novel receptor for Netrin proteins, the Down Syndrome Cell Adhesion Molecule (Dscam). In Down syndrome patients, there is an extra copy of chromosome 21. Although there are several hundred genes on chromosome 21, only a few of those genes are thought to be responsible for the majority of the symptoms. One of these genes is Dscam, a cell adhesion molecule, which allows cells to stick to one another. Dr. Kidd's work has shown that Dscam functions as a Netrin receptor to guide both nerves and cells as they migrate. Dscam also appears to be a receptor for yet to be identified cues that function in the developing nervous system. This adds to our understanding of how spinal cords and brains form, as well as having implications for spinal cord injury, as well as other conditions that impact both nerves and blood vessels such as diabetes. Knowledge that Dscam functions as both a cell adhesion molecule and as a receptor should allow for a greater understanding of how the Down Syndrome phenotype develops, including the congenital heart disease frequently seen in patients.